ArticleGenetics in medicine : official journal of the American College of Medical Genetics2024
Recommendations for risk allele evidence curation, classification, and reporting from the ClinGen Low Penetrance/Risk Allele Working Group.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
48 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Consideration of inherited cancer risk on a continuum: An international and multidisciplinary perspective: A points to consider statement of the American College of Medical Genetics and Genomics (ACMG).Genetics in medicine : official journal of the American College of Medical Genetics · 2026Guideline
- Management of individuals with heterozygous germline pathogenic variants in RAD51C, RAD51D, and BRIP1: A clinical practice resource of the American College of Medical Genetics and Genomics (ACMG).Genetics in medicine : official journal of the American College of Medical Genetics · 2025Guideline
- Consideration of disease penetrance in the selection of secondary findings gene-disease pairs: A policy statement of the American College of Medical Genetics and Genomics (ACMG).Genetics in medicine : official journal of the American College of Medical Genetics · 2024Guideline
- Jeffrey's Insights: Next-generation sequencing for primary immunodeficiency diagnosis, 2019-2025.Journal of human immunity · 2027Article
- Unlocking the Regulatory Genome: Interpreting the Clinical Impact of Noncoding Variants in Genetic Cardiomyopathies.Circulation. Genomic and precision medicine · 2026Review
- Penetrance, effect and causal attribution: which number should be reported for recurrent copy-number variants?European journal of human genetics : EJHG · 2026Article
- Chromosomal Microarray Diagnostic Yield and Copy Number Variants in a Clinically Well-Characterized Cohort with Nonsyndromic Autism Spectrum Disorder from Southern Brazil.Diagnostics (Basel, Switzerland) · 2026Article
- Genome-wide tandem repeat expansions modify schizophrenia risk in the presence of a 22q11.2 deletion.Molecular psychiatry · 2026Article
- Yao syndrome: Report of 3 cases with a family history.JAAD case reports · 2026Article
- Combining multiplexed functional data to improve variant classification.Genome medicine · 2026Article
- When splicing is not all or none: GT>GC 5' splice-site variants as a model for intermediate effects and challenges in variant classification.HGG advances · 2026Article
- The importance and clinical utility of reanalysis of exome and genome sequencing data.Kidney research and clinical practice · 2026Article
- Updates to gene-disease classifications and inheritance patterns for porphyrias.Molecular genetics and metabolism · 2026Article
- Unraveling the Genetic Fabric of Febrile Seizures.Indian journal of pediatrics · 2026Article
- Romosozumab is effective in patients with variants in LRP5, LRP6, or WNT1.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026Article
- Functional assays for BRCA1 and BRCA2 variant analysis: new tools and their applications.NPJ breast cancer · 2026Review
- Creating an atlas of variant effects to resolve variants of uncertain significance and guide cardiovascular medicine.Nature reviews. Cardiology · 2026Review
- Refinement of the classification of DDX41 variants through analysis of aggregated clinical datasets.Leukemia · 2026Article
- Urgent need to recognize that Disease-Causing TP53 variants with atypical penetrance require distinct clinical recommendations.Journal of the National Cancer Institute · 2026Article
- Zygosity-Dependent Phenotypic Spectrum ofHuman mutation · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
28 authors.
Funding
Abstract
purposeGenetic variants at the low end of the penetrance spectrum have historically been challenging to interpret because their high population frequencies exceed the disease prevalence of the associated condition, leading to a lack of clear segregation between the variant and disease. There is currently substantial variation in the classification of these variants, and no formal classification framework has been widely adopted. The Clinical Genome Resource Low Penetrance/Risk Allele Working Group was formed to address these challenges and promote harmonization within the clinical community.
methodsThe work presented here is the product of internal and community Likert-scaled surveys in combination with expert consensus within the Working Group.
resultsWe formally recognize risk alleles and low-penetrance variants as distinct variant classes from those causing highly penetrant disease that require special considerations regarding their clinical classification and reporting. First, we provide a preferred terminology for these variants. Second, we focus on risk alleles and detail considerations for reviewing relevant studies and present a framework for the classification these variants. Finally, we discuss considerations for clinical reporting of risk alleles.
conclusionThese recommendations support harmonized interpretation, classification, and reporting of variants at the low end of the penetrance spectrum.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.